[unreadable] Diabetes is a major healthcare problem that is reaching crisis proportions, and new therapies are urgently needed. We are developing a long-term glucose sensor the size of a bottle cap with battery-operated telemetry for implantation in subcutaneous tissues. The sensor would have unique applications in type 1 diabetes for hypoglycemia warning, insulin dosing, and control of the artificial pancreas. The sensor may also have application for glucose monitoring in type 2 diabetes, caloric and activity management in obesity, and prevention of type 2 diabetes in susceptible individuals. [unreadable] Development of the long-term implantable glucose sensor has been underway for several years. Previous studies have focused on the development of individual sensor components including: stable preparations of immobilzed glucose oxidase and catalase, novel membranes with controlled permeability, electrochemical detectors, implantable electronics and telemetry, signal processing methods, and the hermetic implant housing. Sensors incorporating these components have been tested extensively in vitro and have proven stable. The sensors have been tested extensively as short-term implants in rodents to determine the effects of microvascular perfusion and mass transfer resistance, leading to minor adjustments in sensor design. The sensor and telemetry system have also been implanted for 4-5 months in pigs, and preliminary results demonstrate that the sensor remains responsive to glucose, although the sensitivity can be affected by the foreign body response. [unreadable] It is now time to determine the ultimate sensor lifetime and reliability as an implant in animals before initiating long-term human studies. Sensors will be implanted in pigs for up to 18 months and regular glucose challenges will be performed. Individual sensors will be explanted at regular intervals and characterized extensively to determine the reliability and projected lifetime of individual sensor components. Tissue samples will be collected for extensive histologic analysis. This study will address the last hurdles before human trials. [unreadable] The long-term implantable glucose sensor has an important role in the therapy for diabetes and obesity. The sensor we are developing has undergone systematic engineering analysis, extensive short-term animal tests, and preliminary long-term implant studies. This project will establish the ultimate sensor lifetime and reliability by long-term implant studies in pigs, as the last step before initiating human trials. Diabetes is a major healthcare problem that is reaching crisis proportions, and new therapies are urgently needed. In long-term animal implant tests, we have demonstrated operation of a new glucose sensor that would have unique applications in type 1 diabetes for hypoglycemia warning, insulin dosing, and control of the artificial pancreas. In this Phase I project we propose to complete the few remaining tasks required prior to human clinical evaluation, which is planned for Phase II. [unreadable] [unreadable]